Spatial and Temporal Sensing Limits of Microtubule Polarization in Neuronal Growth Cones by Intracellular Gradients and Forces

Neuronal growth cones are the most sensitive amongst eukaryotic cells in responding to directional chemical cues. Although a dynamic microtubule cytoskeleton has been shown to be essential for growth cone turning, the precise nature of coupling of the spatial cue with microtubule polarization is less understood. Here we present a computational model of microtubule polarization in a turning neuronal growth cone (GC). We explore the limits of directional cues in modifying the spatial polarization of microtubules by testing the role of microtubule dynamics, gradients of regulators and retrograde forces along filopodia. We analyze the steady state and transition behavior of microtubules on being presented with a directional stimulus. The model makes novel predictions about the minimal angular spread of the chemical signal at the growth cone and the fastest polarization times. A regulatory reaction-diffusion network based on the cyclic phosphorylation-dephosphorylation of a regulator predicts that the receptor signal magnitude can generate the maximal polarization of microtubules and not feedback loops or amplifications in the network. Using both the phenomenological and network models we have demonstrated some of the physical limits within which the MT polarization system works in turning neuron.Comment: 7 figures and supplementary materia

Feedbacks from the metabolic network to the genetic network reveal regulatory modules in E. coli and B. subtilis

The genetic regulatory network (GRN) plays a key role in controlling the response of the cell to changes in the environment. Although the structure of GRNs has been the subject of many studies, their large scale structure in the light of feedbacks from the metabolic network (MN) has received relatively little attention. Here we study the causal structure of the GRNs, namely the chain of influence of one component on the other, taking into account feedback from the MN. First we consider the GRNs of E. coli and B. subtilis without feedback from MN and illustrate their causal structure. Next we augment the GRNs with feedback from their respective MNs by including (a) links from genes coding for enzymes to metabolites produced or consumed in reactions catalyzed by those enzymes and (b) links from metabolites to genes coding for transcription factors whose transcriptional activity the metabolites alter by binding to them. We find that the inclusion of feedback from MN into GRN significantly affects its causal structure, in particular the number of levels and relative positions of nodes in the hierarchy, and the number and size of the strongly connected components (SCCs). We then study the functional significance of the SCCs. For this we identify condition specific feedbacks from the MN into the GRN by retaining only those enzymes that are essential for growth in specific environmental conditions simulated via the technique of flux balance analysis (FBA). We find that the SCCs of the GRN augmented by these feedbacks can be ascribed specific functional roles in the organism. Our algorithmic approach thus reveals relatively autonomous subsystems with specific functionality, or regulatory modules in the organism. This automated approach could be useful in identifying biologically relevant modules in other organisms for which network data is available, but whose biology is less well studied.Comment: 15 figure

CONCEPT OF CHARAKOKTA MEDHYARASAYANAS IN AGE RELATED MILD COGNITIVE IMPAIRMENT (MCI)

Life expectancy has increased as a result of advancement in medical science. As a result the number of elderly in the population is also greater than ever and there is a need to tackle their problems. Mild Cognitive Impairment (MCI) is one of the most common clinical manifestations affecting the elderly population. This is a transitional stage between the cognitive decline of normal ageing and the more serious decline in dementia. Timely intervention is awfully important in these cases as they are at a high risk of developing dementia. According to Sarangadhara Acharya, Medha (grasping and retention power) deteriorates after the fourth decade of life and this may be considered as a warning signal for further Smriti (memory) and Buddhi (intellect) deterioration, in the successive years. Ayurveda has a major role to play in this arena. The 'Medhya Rasayanas' are known to be beneficial to improve the intellectual e.g., Mandukparni Swaras, Yashtimadhu Churna with Ksheer, Guduchi Swaras, and Shankhapushpi Kalka. Medhya Rasayana drugs are used for prevention and treatment of mental disorders of all the age groups. These drugs promote the Intellect (Dhi) Retention power (Dhriti), Memory (Smriti). This review discusses about Medhya Rasayanas as a great player for prevention and management of age related cognitive decline

Algebraic Branching Programs, Border Complexity, and Tangent Spaces

Nisan showed in 1991 that the width of a smallest noncommutative single-(source,sink) algebraic branching program (ABP) to compute a noncommutative polynomial is given by the ranks of specific matrices. This means that the set of noncommutative polynomials with ABP width complexity at most $k$ is Zariski-closed, an important property in geometric complexity theory. It follows that approximations cannot help to reduce the required ABP width. It was mentioned by Forbes that this result would probably break when going from single-(source,sink) ABPs to trace ABPs. We prove that this is correct. Moreover, we study the commutative monotone setting and prove a result similar to Nisan, but concerning the analytic closure. We observe the same behavior here: The set of polynomials with ABP width complexity at most $k$ is closed for single-(source,sink) ABPs and not closed for trace ABPs. The proofs reveal an intriguing connection between tangent spaces and the vector space of flows on the ABP. We close with additional observations on VQP and the closure of VNP which allows us to establish a separation between the two classes

Reducing Attack Surface of a Web Application by Open Web Application Security Project Compliance

The attack surface of a system is the amount of application area that is exposed to the adversaries. The overall vulnerability can be reduced by reducing the attack surface of a web application. In this paper, we have considered the web components of two versions of an in-house developed project management web application and the attack surface has been calculated prior and post open web application security project (OWASP) compliance based on a security audit to determine and then compare the security of this Project Management Application. OWASP is an open community to provide free tools and guidelines for application security. It was observed that the attack surface of the software reduced by 45 per cent once it was made OWASP compliant. The vulnerable surface exposed by the code even after OWASP compliance was due to the mandatory access points left in the software to ensure accessibility over a network.Defence Science Journal, 2012, 62(5), pp.324-330, DOI:http://dx.doi.org/10.14429/dsj.62.129

Homomorphism Polynomials Complete for VP

The VP versus VNP question, introduced by Valiant, is probably the most important open question in algebraic complexity theory. Thanks to completeness results, a variant of this question, VBP versus VNP, can be succinctly restated as asking whether the permanent of a generic matrix can be written as a determinant of a matrix of polynomially bounded size. Strikingly, this restatement does not mention any notion of computational model. To get a similar restatement for the original and more fundamental question, and also to better understand the class itself, we need a complete polynomial for VP. Ad hoc constructions yielding complete polynomials were known, but not natural examples in the vein of the determinant. We give here several variants of natural complete polynomials for VP, based on the notion of graph homomorphism polynomials

SERVER-SIDE COOKIE MANAGEMENT AND CONTROL

Cookie generation may be performed differently depending on the location of the requesting device and a time since a most recent login to a trusted server. For example, if a user has logged in recently, then a server-side mapping may be accurate and a mapped cookie may be utilized

Unravelling the unseen ‘C’ with the cone beam computed tomography: a rare case report

Recognition of aberrant root canal configurations is critical to successfully negotiate and treat a canal and one of such aberrancies is a C shape root canal system. The fins and webs present in a C shape canal system presents a challenge to debridement and obturation. Knowledge of variations through advanced imaging modalities like CBCT, rotary and hand instruments assisted with ultrasonics and modified obturation techniques aid in effective management of C shaped root canals. This case report presents a successful endodontic management of a rare c shape canal configuration in a mandibular second premolar with the aid of the cone‑beam computed tomography (CBCT) scanning imaging technique